chr22-36864062-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000631.5(NCF4):c.50C>T(p.Pro17Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00013 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P17P) has been classified as Likely benign.
Frequency
Consequence
NM_000631.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCF4 | NM_000631.5 | c.50C>T | p.Pro17Leu | missense_variant | 2/10 | ENST00000248899.11 | |
NCF4-AS1 | NR_147197.1 | n.351+6031G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCF4 | ENST00000248899.11 | c.50C>T | p.Pro17Leu | missense_variant | 2/10 | 1 | NM_000631.5 | P1 | |
NCF4-AS1 | ENST00000619915.1 | n.349+6031G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000191 AC: 29AN: 152162Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.000103 AC: 26AN: 251496Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135922
GnomAD4 exome AF: 0.000124 AC: 181AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.000120 AC XY: 87AN XY: 727240
GnomAD4 genome ? AF: 0.000191 AC: 29AN: 152162Hom.: 0 Cov.: 30 AF XY: 0.000175 AC XY: 13AN XY: 74334
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 25, 2022 | The c.50C>T (p.P17L) alteration is located in exon 2 (coding exon 2) of the NCF4 gene. This alteration results from a C to T substitution at nucleotide position 50, causing the proline (P) at amino acid position 17 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 17 of the NCF4 protein (p.Pro17Leu). This variant is present in population databases (rs147322774, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with NCF4-related conditions. ClinVar contains an entry for this variant (Variation ID: 661385). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at